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  • Evaluation of amnion-derived mesenchymal stem cells for treatment-resistant moderate Crohn’s disease: study protocol for a phase I/II, dual-centre, open-label, uncontrolled, dose–response trial

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Inflammatory bowel disease
Evaluation of amnion-derived mesenchymal stem cells for treatment-resistant moderate Crohn’s disease: study protocol for a phase I/II, dual-centre, open-label, uncontrolled, dose–response trial
  1. Shinsuke Otagiri1,
  2. Shunsuke Ohnishi1,
  3. Arisa Miura2,
  4. Hiroshi Hayashi2,
  5. Izumi Kumagai2,
  6. Yoichi M Ito3,
  7. Takehiko Katsurada1,
  8. Shiro Nakamura4,
  9. Rika Okamoto5,
  10. Kenichi Yamahara6,
  11. Kyu Yong Cho2,
  12. Toshiyuki Isoe2,
  13. Norihiro Sato2,
  14. Naoya Sakamoto1
  1. 1 Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  2. 2 Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan
  3. 3 Department of Biostatistics, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  4. 4 Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan
  5. 5 Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Japan
  6. 6 Department of Transfusion Medicine and Cell Therapy, Hyogo College of Medicine, Nishinomiya, Japan
  1. Correspondence to Dr Shunsuke Ohnishi; sonishi{at}pop.med.hokudai.ac.jp

Abstract

Introduction The medical treatment options for patients with Crohn’s disease (CD) are limited and patients resistant to those therapies are left requiring surgical operations that usually only achieve some symptomatic relief. Mesenchymal stem cells (MSC) have been shown to be effective for the treatment of CD, and we have demonstrated in animal experiments that human amnion-derived MSCs (AMSC) are a potential new therapeutic strategy. Therefore, we designed this study to investigate the safety and efficacy of AMSCs in patients with treatment-resistant CD.

Methods and analysis This is the protocol for an ongoing phase I/II, dual-centre, open-label, uncontrolled, dose–response study. The estimated enrolment is 6–12 patients with treatment-resistant, moderate CD. A dose of 1.0×106 cells/kg will be administered intravenously in the low-dose group at days 0 and 7. After confirming the safety of low-dose administration, a dose of 4.0×106 cells/kg will be administered intravenously in the high-dose group on days 0 and 7. The primary endpoint will measure the occurrence of adverse events related to acute infusion toxicity, and secondary endpoints will include long-term adverse events and efficacy of AMSC administration.

Ethics and dissemination The Institutional Review Board of Hokkaido University Hospital approved this study protocol (approval number H29-6). A report releasing study results will be submitted to an appropriate journal.

Discussion This study is the first to investigate the safety and efficacy of AMSC use for CD treatment. Our results will advance studies on more efficient and convenient methods to overcome the limits of available CD treatments.

Trial registration number UMIN000029841.

  • Crohn’s disease
  • stem cells
  • bacterial interactions

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjgast-2018-000206

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    Footnotes

    • Contributors SOt contributed by writing the manuscript and in carrying out the trial. SOh is the principal investigator, responsible for conception, design, and processing of the trial. AM, HH, IK, and TI reviewed all protocol versions and contributed to the start-up of the trial. YMI contributed to the design of the trial and the statistical analysis plan. TK and SN contributed by reviewing all protocol versions and carrying out the trial. KY reviewed all protocol versions and was involved in manufacturing and quality control of AM01. NSat and NSak supervised and edited the protocol.

    • Funding This work was supported by the Research Project for Applications of Regenerative Medicine from the Japan Agency of Medical Research and Development (AMED, 17bk0104058h0002).

    • Competing interests None declared.

    • Patient consent Not required.

    • Ethics approval Institutional Review Board of Hokkaido University Hospital (approval number H29-6).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement We will share the data after the trial is finished. Additional details of the study protocol can be requested from the corresponding author.